Optical measurement of hematocrit and other biological constituents in renal therapy.

Optical sensors have advanced significantly over the past 2 decades leading to today's noninvasive optical measurement capabilities and their widespread applications in renal therapy. These measurements provide significant advantages to the clinician. For example, a given blood constituent can be monitored in real time (continuously, nondestructively), which facilitates the ability to optimally "titrate" the therapy with immediate visual feedback. Optical methods have another intrinsic advantage in that each biologic constituent has its own unique spectral "signature" allowing for simultaneous, multiple, and specific measurements of biologic analytes. Use of this budding spectral technology in renal therapy today provides for increased patient safety (by measuring plasma-free hemoglobin, microemboli, clots, oxygen saturation, blood leaks, and hematocrit), measurements of dialysis dose (dialysate urea levels), dry weight (tissue water monitoring), access viability (recirculation, access blood flow), cardiac status (absolute blood volume, cardiac output), and enhanced continuous fluid management (fluid overload, critical blood volume). As microelectronics and signal processing capabilities continue to advance, so will the future of optical diagnosis and treatment. These capabilities translate directly to improved patient quality of life.

Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations.

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6-48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05-0.3 microM thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7-3.0 microM thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 microM, respectively).